The team searched the medical literature in 2013 using MEDLINE/Pubmed, Embase, Cochrane Library, and Web of Science/Scopus for randomized, controlled trials of highly selective 5-HT4 agonists in adults with chronic constipation, with no minimum duration of therapy or date limitations.

The researchers' main outcomes included stool frequency, Patient-Assessment of Constipation Quality of Life (PAC-QOL), PAC of symptoms (PAC-SYM) and adverse events.

The team identified 13 eligible trials, including 11 on prucalopride, 1 on velusetrag, and 1 on naronapride.

Adverse events were more common with highly selective 5-HT4 agonists

Alimentary Pharmacology & Therapeutics

Relative to control, treatment with highly selective 5-HT4 agonists was superior for all outcomes.

The team noted that the only active comparator trial of prucalopride and PEG3350 suggested PEG3350 is more efficacious for some end points.

The researchers observed that adverse events were more common with highly selective 5-HT4 agonists, but were generally minor.

Headache was the most frequent advers event.

The team found that most trials studied prucalopride.

Dr Camilleri's team concluded, "Demonstration of efficacy on patient-important outcomes and a favorable safety profile support the continued use and development of highly selective 5–HT4 agonists in the treatment of chronic constipation."